KR20040032822A - Photodynamic therapy lamp - Google Patents

Abstract

The photodynamic therapeutic lamp has a lid 10, 11, 12, 13, which has a light source formed from two arrays 20 of LEDs 21. The LEDs are arranged in a honeycomb pattern and have a peak wavelength of 630-640 nm. Below the LED is a lens pack 22 with a lens 23 for each LED. Underneath is the diffuser 7. The lenses are arranged in a honeycomb pattern and serve to focus the light in a substantially parallel and narrow beam.

Description

Photodynamic therapy lamp

Photodynamic therapy (PDT) is an evolving therapy and is used today for the treatment of various cancers, and also for the treatment of infections, wounds, and non-malignant diseases, including various dermatological diseases. Such a method is based on the interaction of oxygen with a specific photosensitizer of light. Clinical experience has shown that PDT has advantages over other therapies for the treatment of some pathological conditions, such as keratin fibers in acne and various skin cancers. General background of clinical use of PDT can be found in US 6,225,333, US 6,136,841, US 6,107,466, US 6,036,941, US 5,965,598 and US 5,952,329.

Several photosensors are commercially available and include 5-aminolevulinic acid (5-ALA), 5-ALA derivatives, and porphyrin derivatives before or during clinical development. have. Other photosensitizers have been proposed in the prior art, for example, in Harurot, M et al., FASEB journals 15, 612 (Neurologia, Neurochiirurgia Polska 34,973 (2000)). 2001, Pervaiz, S., and Therapeutische Umschau 58, 28 (2001), Corner-Stifbold, U., and Brit J. Obsmolology (Brit. J. Ophthalmology 85, 483 (2001), Sobrane, G. et al., J. Fr. Despettre, T., et al., Ophthalomologie 24, 82 (2001), Barr at Alimentary Pharmacology & Therapeutics 15, 311 (2001). ), H. et al., Schmidt-Erfurth, U et al., In Ophthalmologie 98, 216 (2001), and Rockson, SG, in Circulation 102, 591 (2000). And others have been disclosed.

One important element in a safe and effective PDT is the light source. Clinically useful light sources must meet several criteria. The intensity of the light must be high (ie high emission flux); It should be easy to set the light dose of light; There must be a peak wavelength of the emission spectrum within the region of interest; There must be a uniform emitted light intensity within the region of interest; Its low cost of operation and its simple construction must have a reliable configuration.

There are several light sources for PDTs disclosed in the prior art. US 5,441,531 (DUSA) discloses a method for PDT comprising the step of including a filter and a dichroic mirror to select the correct wavelength and eliminate infrared radiation, and US 5,782,895 (DUSA) Illuminators for PDTs with holders, filters, and dichroic mirrors are disclosed, US Pat. No. 5,961,543 (Herbert Waldman) discloses a lamp reflector, a filter device and a device for PDT irradiation with a pair of blowers, US 5,634,711 (Kennedy) discloses a portable light irradiation device for PDT, US 5,798,523 (Theratechnologies) discloses a motorized device for PDT, and US 5,843,143 (Cancer Research Campaign Technology) has more than 75 mW per square centimeter. Claims are made for a non-laser light source with a high intensity lamp having an output intensity and a band in the range of 0 to 30 Nm, US Pat. A non-coherent electromagnetic energy source capable of generating a wide range of wavelength irradiation energy of W is disclosed, US 6,007,225 (Advanced Otical Technologies) discloses an oriented illumination system using a conical light deflector, US 6,048,359 (Advanced Photodynamic Technologies) disclose a method and apparatus for an optical system for the diagnosis of skin diseases, and US Pat. No. 6,096,066 (Light Science Limited Partnership) for a light therapy patch, US 6,128,525 (Zeng et al) An apparatus for controlling dosimetry of PDT is disclosed, and WO 00/00250 (Genetronics) discloses an apparatus for electroporation of cells and light activation of electroporated ceps. . WO 99/10046 (Advanvced Photodynamic Technologies) discloses a light irradiation treatment apparatus having a shell and a liner made of a polymeric material. WO 98/04317 (Light Science Limited Partnership) proposes a device for applying fever therapy to improve the efficiency of light therapy, and WO 85/00527 (M. Utzhas) proposes a plurality of filters, particularly for dermatological applications. An excitation irradiation device is disclosed, WO 99/56827 (DUSA) discloses a light source for a contoured surface with a plurality of light sources, and EPO 604 931 (Matushita Electric Industrial Co.) a medical laser device. WO 99/06113 (Zeng et al.) Discloses a device for controlling the dosimetry of PDTs, and WO 84/00101 (The John Hopkins University) describes the effects of PDT and provides an accurate An apparatus for prescribing light quantity is disclosed. WO 45/32441 (United States Government) discloses an optical transmission device having an optical fiber, and WO 00/25866 (Garat) discloses an incoherent optical energy with filtering and focusing means for generating radiation energy in a wide band. An apparatus for PDT using a source of is disclosed.

Other devices of photodynamic therapy include US 4,576,173 (Johns Hopkips University), US 4,592,361 (Johns Hopkins University), US 4,973,848 (J. McCaugahn), US 5,298,742 (Dep. Health, USA), US 5,474,528 (Dusa), US 5,489,279 (US 5,489,279) DISA, US 5,500,009 (Amron), US 5,505,726 (DUSA), US 5,519,435 (US Government), US 5,521,392 (EFOS), US 5,533,508 (PDT Systems), US 5,643,334 (ESC Medical Systems Limited) and US 5,814,008 (Light Science Limited) Partnership.

Instead of using a conventional lamp, several patents of the prior art propose a lamp for photodynamic therapy based on light emitting diodes (LEDS). See, for example, WO 94/15666 (PDT system), FR 2492666 (Maret), WO 95/19812 (Markham), US 5,259,380 (Amcor), EP 0266038 (Kureha Kagaku Kogyo), US 5,698,866 (PDT system), US 5,420,768 (Kennedy), US 5,549,660 (Amron), and US 6,048,359 (AdvancedPhotodynamic Technologies).

It is believed that there are many advantages to using LED technology instead of using conventional lamps. For example, an array of LEDs can be formed to cover a large area. Moreover, its high efficiency ensures that less heat dissipation is required. In addition, the LEDs have long-term stability and therefore it is easy to design a lamp suitable for tens of thousands of hours of operation. Other advantages are low cost of operation and maintenance, low drive voltage to increase stability, their mechanically robust characteristics, light weight intensively modular construction, and ease of movement and transmission.

However, despite these significant advantages, there are some drawbacks to using the LED technology disclosed in the prior art for photodynamic therapy, which impacts the utility of LED lamps in PDT.

The main disadvantage of using LED lamps in a two-dimensional arrangement is that the light uniformity is not good enough to obtain a safe and effective PDT treatment. This is because the light pattern from the LEDs may be in the shape of a bat wing, for example with a wide output angle. Other disadvantages of using the known PDT-LED technology include the following. Because of the need for liquid-based cooling systems, they have a relatively high cost and complexity, have a relatively broad light spectrum (600-700 nm) and have a limited light output resulting in long treatment times.

The present invention relates to an illuminator source (also referred to as a lamp) used for photodynamic therapy (PDT).

1 is a perspective view of a first embodiment of the present invention and shows a mounting arm thereof.

2 is a perspective view from below of the first embodiment of FIG. 1;

3 is a perspective view from above of the embodiment of FIG. 1;

4 is an exploded view (corresponding to FIG. 2) of the embodiment of FIG. 1.

5 is an exploded view of the embodiment of FIG. 1 seen from one side below.

6 is an exploded view of the embodiment of FIG. 1 seen from below and from one side;

7 is a perspective view from above of a second embodiment of the present invention and shows a mounting arm thereof;

8 is a perspective view from below of the embodiment of FIG. 7;

9 is a perspective view from below of the embodiment of FIG. 7;

10 is an exploded view from above of the embodiment of FIG. 7;

FIG. 11 is an exploded view from below of the embodiment of FIG. 7; FIG.

12 is a schematic diagram of light rays representing the optics used in both embodiments.

13 is a schematic diagram illustrating placement of LEDs in embodiments.

14 is a perspective view of a lens used in embodiments.

15A and 15B show the effect of the lens used in the embodiments of the present invention.

16 shows the effect of LED junction temperature varying in peak wavelength.

According to the present invention there is provided a radiation source for use in photodynamic therapy comprising a two-dimensional array of LEDs (light emitting diodes) and further comprising means for focusing the light emitted from the LEDs.

By focusing light in this way, the variation in light intensity with distance from the irradiation source is greatly reduced, which means that the distance between the patient and the light source does not have a decisive effect on the amount of light received. All of these simplify the treatment and allow for effective and uniform treatment of non-planar surfaces. Moreover, the light intensity is increased even at a considerable distance from the source and the present invention also allows a much more uniform irradiation pattern to be generated.

Focusing is most effectively achieved by using lenses with LEDs and is most desirable where each LED lamp has an associated additional lens system. In this way the most uniform light can be obtained at any working distance from the body.

Although multiple element lenses can be used, a single additional lens is preferably provided for each LED. Preferred lenses used in the present invention are lenses that can orient light in order to ensure uniform light intensity over the area of interest. Typical lenses are lenses made of synthetic materials or glass. The most preferred type of lens is an axicon focused light guide. Such lenses are most desirable because they are designed to reduce the scattering effect of losing light outside the vicinity of the focused beam.

Although the devices described so far offer significant advantages over the prior art, the lens systems are joined together in a hexagonal pattern, preferably on a diode matrix, to further ensure a wider optical field of uniform properties. It is desirable to be made of a hexagonal lens unit that can be packed in close proximity. Thus, the individual lenses are preferably hexagonal or substantially hexagonal in plane. This is believed to be inventive in itself and therefore from another aspect of the invention the present invention provides a PDT lamp with an array of hexagonal lenses as a whole arranged in a honeycomb pattern.

The change in light intensity over the site of interest should be less than +/- 15%, preferably less than +/- 10%, most preferably less than +/- 7%.

Although lower power can be used if desired, the source according to the invention preferably provides at least 20 mW / cm ² . It is also desirable that the output is no greater than 100 mW / cm ² at a nominal distance of 5 cm based on the Full Width Half Maximum (FWHM) of about 18 nm. Preferably the power is no greater than 40 mW / cm ² at a distance of 5 cm to avoid long treatment times.

Although the actual number of LEDs is between 1 and 3000, the number of LEDs may vary depending on the irradiation area. The most preferred number is between 4 and 512 and the most preferred number is between 8 and 256 LEDs.

The irradiation area may vary depending on the placement of the lens and the number of LEDs, but this is preferably between 1 m ² and 3000 cm ² .

The lamp for irradiation of 40 mm X 50 mm may for example have 16 diodes. A lamp for irradiation of 90 mm X 190 mm may for example have 128 diodes. The distance between the diodes is preferably in the range of 2 mm to 20 mm depending on the intensity of the light.

To be useful in PDT, the peak wavelength of the light is preferably 625-640 nm, most preferably 630-640 nm, for example used with Photoporphyrin IX. However, the lamps have other light such as Photofrin, Phorphycenes, Sn-Etiopurin, m-THPC, NpE6, Zn-phthalocyanine and Benzoporphyrin. Different LEDs covering the peak portion of the sensory agent may have different wavelengths.

Although lamp-based LEDs generate less heat on their own than other types of light sources, the lamp may optionally be equipped with a patient fan to cool the patient's target affected area. Preferably it is combined with a cooling system for the lamp itself. Thus, for example, the lamp is provided with a cooling fan, which exits the lamp in the entire direction, such as the irradiated light, to cool the LEDs (directly or indirectly) and to allow the irradiated portion of the patient to cool. Orient the air to both sides.

The diodes are preferably associated with a heat sink which can in turn be cooled by the flow of air provided by the fan. This can be controlled by a continuous or simple thermostatic switch, but is preferably controlled by a microprocessor, for example based on input from a temperature sensor. If desired, the temperature of the LEDs can be controlled to change the peak output frequency. Such control may be provided by NTC registers, for example providing input to the microprocessor. Typical frequency change is 0.2 nm / K.

This concept is believed to be inventive on its own, and accordingly another feature provides a light source for use in PDTs where the light source comprises an array of LEDs and the output frequency of the LEDs is varied by controlling their temperature. .

Preferably, additionally or alternatively, the lamp is microprocessor controlled such that a dose timer and / or a timer that determines the life of the lamp (based on the overall time of use) can be provided. An automatic distance measuring instrument may also be provided so that the irradiation dose can be adjusted (automatically or manually) to correct for the remaining change in light intensity with distance from the source.

In addition, means for modulation of the light source can again be provided, preferably under microprocessor control, so that the amplitude or frequency of the light can be changed over time, for example in accordance with a program stored in a computer memory. Such modulation can provide much more effective processing in certain situations. For example, a pulse train of light followed by a brief pause allows the cell to pick up more oxygen. Preferably the user can program the modulation. The provision of a modifiable lamp is believed to be inventive in itself (preferably just described) and forms another feature of the invention. Thus, in view of another feature of the present invention, there is provided a lamp for a PDT having a plurality of LED light sources that can be modulated during use.

Another preferred feature is the provision of dividing means for reducing the illuminated area. Thus, for example, eight groups of LEDs can be selectively deactivated or a mask can be provided in the lamp to prevent light from the selected LEDs from reaching the patient.

Although the light provided by the present invention and particularly provided as its preferred form may be sufficiently uniform for any PDT application, by providing a mechanical vibration of the LED so that each focused beam moves over the target surface Uniformity can be further improved. It will be appreciated that only a small amount of movement is required to move the beam axis of one beam halfway toward a point defined on the target by, for example, the previous position of the beam axis of the adjacent beam (ie, the position before the movement). will be. Again, this concept is believed to be independently inventive and provides a lamp for a PDT having an arrangement of light sources arranged to vibrate when viewed as another feature of the present invention, and according to another feature of the present invention. .

The present invention also extends to a method of providing a PDT, and thus provides a method of a PDT that includes the use of a lamp or light source in accordance with any other aspect of the invention when viewed in another aspect of the invention. Preferably such a method comprises the use of a lamp or source according to a preferred form of the invention.

Specific embodiments of the present invention will be described as only one example with reference to the accompanying drawings.

Referring to FIG. 1, the phototherapy lamp 1 consists of a balanced support arm 2 with a lamp (not shown), an external power supply (not shown), and a lamp head 3. While this figure shows the first embodiment of the present invention, a similar arm is provided for the second embodiment (see FIG. 7). The arm allows the lamp to be fixed to a surface, for example a table in a doctor's consultation room. The arm is substantially conventional and allows the lamp head to move to a position above the body part of the patient to be treated.

Referring now to FIG. 2, the lamp head 3 of the first embodiment may be shown to be pivotally mounted to the side arm 2a. The side arms are shaped to generally conform to the outer shape of the lamp head. (This is more clearly seen in FIG. 5, where the side arm 2a is shown engaged with the pivot pin 2c.) The side arm itself is via the swivel joint 4. Is connected to (2b). The rotary ring joint 4 allows movement about two perpendicular axes and the pivotal mounting of the side arms to the lamp head provides additional movement.

The housing 6 has an opening in its lower surface where the light source 5 can be seen through the thin diffuser 7. It can be seen from FIG. 3 that an air outlet 8 is provided in the upper part of the housing 6, which is in the form of a ventilation slot formed in the housing itself.

Referring now to FIGS. 4-6, the housing 6 is formed from several molded plastic components, which have an upper cover 10, a lower cover 11, and end covers 12, 13. The end covers are provided with ventilation slots to allow the flow of air through the lamp during use, with the ventilation slots on the end cover 13 being the air intake and the ventilation slots on the end cover 12 being the outlet.

Inside the housing is a light source consisting of several LEDs, a control unit, a cooling system and a lens system provided in the housing. These components will be described in more detail later.

The light source is formed from two arrays 20 of modules, each with 64 LEDs 21. The LEDs are arranged in a honeycomb pattern (ie hexagonal arrangement) as shown in FIG. The LEDs each have a peak wavelength in the range of 630-640 nm and an output of 60 W / cm ₂ at 5 cm.

Below the LED array 20 is a lens pack 22 with a lens 23 for each LED. Underneath is again a thin diffusion 7, which is located in the recess in the opening in the lower lid 11.

FIG. 14 shows one of the lenses 23 and FIG. 12 is a diagram of the light beam showing its operation. LED 21 is at the bottom of the figure and lens 23 is above it. The diffuser 7 is omitted for clarity of the drawing. As can be seen from the ray diagram, substantially all of the light from the LED 21 is concentrated substantially parallel so that a narrow beam is centered on the lens and the optical axis of the LED. As will be described later, the effects of the lenses are shown in FIGS. 15A and 15B.

The current to the LED module is provided by a conventional power supply and will therefore not be described further through the control unit 25 based on the microprocessor. In addition to controlling the supply of current to the LEDs 21, the control unit also controls the electric cooling fan 27 and various other features such as lamp life monitors, dose timers and the like.

In order to maintain the desired output radiation frequency, it is important that the LEDs 21 are not too warm but can be controlled at a stable temperature. The fan is thus part of an air cooling system further comprising a heat sink 28 mounted to the back of the LED panel. The fan forces the air to move through the cooling ribs through the air intake in the cover 13, over the LED array 20 and out through the outlet in the cover 12. The operating temperature is sensed via a sensor (not shown) and a feedback system is provided for the microprocessor to control this temperature.

If desired, the temperature of the LEDs can be varied to adjust the output peak wavelength of the LED. There is an approximately linear relationship between the LED junction temperature and the wavelength. 16 shows experimental results showing it. In this experiment, the spectrum of the LED at different LED junction temperatures was recorded and the peak wavelength was plotted against the LED junction temperature. It is shown in FIG. 16 that the peak wavelength is proportional to the junction temperature. The most linear fit for the data point gives a proportion of 0.208 nm per 1 ° C. Thus, the junction temperature can be controlled in the LED lamp and ensures overlap between the absorption spectrum of the photosensitive agent (eg, protoporphyrin IX) and the LED irradiation spectrum.

The flow of air is effectively divided into two paths upon intake. One path is directed to the heat sink 28 and the other path is arranged to blow air over the patient's skin. This provides a cooling effect that relieves the pain introduced by the action of the chemical.

In use, the lamp is secured to the surface via arms 2a and 2b and clamps (not shown). The lamp is positioned above the skin area of the patient to be irradiated next.

Control over the lamp is found in the control panel / display unit 9.

The system is switched on and off by pressing the on / off button. When the system is left on, the button remains pressed until "CURELIGHT V x.x, Ser.no:0100XXXX" appears in the display window. After a few seconds, "REMAINING LAMP LIFE XXhXX" is displayed. This represents the remaining full light operating time, expressed in hours and minutes as the microprocessor calculates. When the timer indicates 0h00, no further use is possible. A dose timer is also provided to indicate how long the lamp will be on for a particular treatment time.

The system is switched off by pressing the on / off button once again. When the button is pressed, it beeps and the system is switched off.

To accurately position the lamp in the area to be treated, the operator presses the GUIDE LIGHT button to cause the lamp to be switched on at low power. The lamp can then move so that the correct part of the skin is under illumination. Although the current value of the dose timer is not shown, the timers will not be affected in the low light mode. Normally, if subsequent full light treatment has not been stopped, this timer will be 0:00. By pressing the GUIDE LIGHT button once again, the light is switched off.

If the lamp was in FULL LIGHT mode before pressing the GUIDE LIGHT button, the lamp will switch to the guide light and the timer will stop.

A PAUSE button may also be provided to be used to temporarily stop the treatment. Pressing this button again will continue treatment from where it was left.

There is also a MODE BUTTON used to select the SET DOSE function to adjust the dose of light, if necessary. The buttons are used with the dose setting function to adjust the value of the dose. The +/- buttons adjust the dose in steps of 1 J / cm ² and the corresponding dose time will be calculated and displayed simultaneously as minutes and hours. By pressing and holding the buttons, a rapid rise or fall adjustment will occur. A light dose of 37 J / cm ² is believed to be the most effective. The mode button may be used to activate other functions, such as to reduce the segment of the illuminated area (less treatment area).

After the lamp is correctly positioned, the operator presses the START button to convert the lamp to treatment intensity. Dose timers and ramp timers will read in seconds when the lamp is in full light mode. Only the dose timer is displayed.

When the dose timer goes to 0:00, the light is automatically switched off and a flashing message such as "END OF DOSE" is displayed. The pulsating sound is emitted until the RESET button (see below) is pressed.

The stop / reset button can be used to stop the continued operation or to clear the "end of dosing" or error message.

The second embodiment of the present invention is similar to the first embodiment in most operational features, although it has a different appearance and structure as can be seen in FIGS. 7 to 11. In particular, the housing is effectively rotated 90 degrees so that the arm 2 is connected via the rotary ring joint 4 directly to the side of the housing without the side arm. Moreover, the inlet and outlet of the air are provided in the end covers 12, 13, which are found here on the opposite side of the joint 4.

As can be seen in FIGS. 10 and 11, the lamp head 3 has a housing with two end covers 12 and 13 and a front and back cover (not shown in the figures for clarity). It is formed from.

FIG. 11 best shows the light source device, which has a thin diffuser 7, a lens array 22, an LED array 20, and a heat sink 28 as in the previous embodiment. However, it will be appreciated that the number of LEDs and lenses is much reduced and therefore such lamps are intended for use in smaller areas of the skin. The additional portion of the lid forms a portion 29 surrounding the light.

To the far left of the figure, the fan 27 draws air through the intake and, as previously described, directs the fins of the heat sink 28.

On top of the heat sink, a control system and a display are provided. These are more clearly shown in FIG.

The lamp of the second embodiment is operated in the same manner as described above in connection with the first embodiment.

Finally, an example of one of the lenses used in both embodiments is shown in FIG. 14. The lenses have a hexagonal outer shape so that they can be packaged in the hexagonal (honeycomb) arrangement shown in FIG. The lens is an axicon collimating lightguide and is shaped to provide a substantial focusing beam as shown in FIG. 12.

15A and 15B show the results of the experiment to show the effect of the lens array 22. A lens array LED array (FIG. 15A) and a lens array LED array (FIG. 15B) were placed under frosted glass and photographed at the same distance between the frosted glass and the camera. As can be seen from FIG. 15A, the lenses focus the light into a defined shield, while in FIG. 15B the light is much more dispersed.

As previously described, the distance between the lamp and the patient is not critical to the delivered dose (light energy) because the beam is effectively focused. This not only means that the lamp does not need to be positioned at the correct distance from the patient's skin, but also means that uneven surfaces can be effectively treated without significant change in dosage between elevated and low sites. .

The invention can be used in PDT treatment.

Claims (14)

An irradiation source for use in photodynamic treatment regimens having a two-dimensional array of LEDs (light emitting diodes) and further comprising means for focusing the light emitted from the LEDs. The method of claim 1, Each LED lamp has an associated additional lens system. The method of claim 2, A source for illumination, characterized in that a single additional lens is provided for each LED. The method of claim 3, wherein And the individual lenses are hexagonal or substantially hexagonal in plane. The method of claim 4, wherein The lens system preferably comprises a hexagonal lens unit packaged closely together in a hexagonal pattern. The method of claim 1, wherein The lamp is controlled by a microprocessor such that a dose timer and / or a timer for determining the life of the lamp is provided. The method of claim 1, wherein The lamp further comprises a patient pan for cooling the target site of the patient. The method of claim 7, wherein The patient pan is combined with a cooling system for the lamp itself. The method according to claim 7 or 8, The lamp has a cooling fan such that the cooling fan orients the air to both sides to exit the lamp in the same general direction as the irradiated light such that the cooling fan cools the LED and the irradiated portion of the patient can be cooled. Research source. The method of claim 1, wherein The flow of air is provided to control the temperature of the diode, and the flow of air is controlled by a microprocessor. The method of claim 1, wherein The output frequency of the LEDs is characterized by being converted by controlling their temperature. The method of claim 1, wherein An irradiation source is characterized in that the light source is modifiable. The method of claim 12, Wherein the amplitude or frequency of the light is modulated under microprocessor control. A photodynamic therapy method comprising the use of an irradiation source according to the preceding terms.